WO2007027164A1

WO2007027164A1 - Method and device for the macular degeneration treatment

Info

Publication number: WO2007027164A1
Application number: PCT/UA2005/000057
Authority: WO
Inventors: Leonid Andriyovych Linnik; Olexander Stanislavovych Pekaryk
Original assignee: Leonid Andriyovych Linnik; Pekaryk Olexander Stanislavovy
Priority date: 2005-08-31
Filing date: 2005-12-14
Publication date: 2007-03-08
Also published as: UA80467C2; US20080234668A1; RU2008108422A; CA2621048A1; CN101296676B; EP1937197A1; CA2621048C; EP1937197A4; CN101296676A

Abstract

The present concerns ophthalmology. This invention can be used for the treatment of retina degeneration diseases, particularly for macular degeneration treatment. A method of the macula degeneration treatment by irradiating of the retina damaged areas through the pupil wherein the technique of the irradiation performed by the quasi-monochromatic light pulse in visible and near infra-red spectral range with energy that does not exceed 10-5 joules. A device for the macula degeneration treatment that consists of radiation source, radiation directional pattern forming means, means to deliver the radiation to the given part of the retina through the pupil, power supply unit, and indicator and control unit; the device comprising at least one light emitting diode (LED) is used as the source of radiation.

Description

METHOD AND DEVICE FOR THE MACULAR DEGENERATION TREATMENT

The present invention relates to a device and a method for medicine and concerns ophthalmology. This invention can be used for the treatment of retina degeneration diseases, particularly for macular degeneration treatment.

The method of macular degeneration (MD) treatment by low-energy X-ray radiation is known. Radiotherapy system TheraSight Ocular Brachytherapy System, suggested by Theragenics Corporation, for implementation of this method is on the stage of clinical trials and there are no certain data available concerning the results of it appliance. ("Radiotherapy in age-related macular degeneration", Gripp, S.; Stammen, J.; Petersen, C; Hartmann, A.; Willers, R. ; Althaus, C, Int. J. Radiat. Oncol. Biol. Phys . 2002 Feb 1; 52 (2) : 489-95)

The other known method of macular degeneration treatment is transpupillary thermotherapy (TTT) . TTT is a technique in which heat is delivered to the choroids and retinal pigment epithelium through the pupil using diode laser in combination with drug therapy. This method is developed and introduced by IRIDEX Company. Special device for the method realization includes an infrared CW laser. This method is developed for the "wet" or neovascular form of MD treatment. But there is no information on applicability of the TTT method to the treatment of "dry" or non-neovascular form of MD.

("Transpupillary thermotherapy of juxtafoveal recurrent choroidal neovascularization" Cardillo-Piccolino, -F; Eandi,- C-M; Ventre,-L; Rigault-De-La-Longrais, -R-C; Grignolo, -F-M, Eur-J-Ophthalmol. 2003 Jun; 13(5): 453-60; web site of IRIDEX company - www.iredex.com) .

A drawback of above method is the use of substantial radiation power to ensure necessary thermal action that increases a risk of unforeseen permanent damage of the eye tissue. Though the energy values at the eye bottom are less then threshold level, there is real danger of thermal injury of eye tissues. In the proposed method and device energy level is much lower then the threshold level and thus the probability of thermal injury of the eye tissue are diminished.

The closest prior art to the present invention by the physical principles and medical effect is a method of photodynamic therapy (PDT) in the so called "wet" form of MD treatment by which the retina of the eye is underwent irradiation by laser radiation with the energy that is lower then the energy needed for the retina tissue coagulation. Under such conditions the changes initiated by light are taking place within the eye tissues at the biochemical level of cells functioning. In PDT method for increasing light efficiency the use chemical optical sensitizer (Visudyne, Novartis) is indispensable.

An optical sensitizer selectively magnifies absorption of laser light by the eye tissues. There are special types of optical sensitizers for each laser used in process. Visudyne delivered to the retina vessels by intravenous injection. Using Visudyne, 16% of the patients have the improvement in visual acuity (VA) that is almost twice as much that in those who did not undergo PTD with Visudyne. The VISULASTM 690s system by Carl Zeiss Meditiec Company (see the company booklet) that realizes the PDT method can be considered as the closest prior art of the proposed device.

The energy that affects eye tissues by using the above method remains high enough. Furthermore, this method requires the injection of optical sensitizer in the patient's blood and this has a toxic impact upon the human organism as a whole. (Novartis - http://www.novartis.com/; Carl Zeiss Meditec AG - http: //www.meditec. zeiss.com; Booklets of Carl Zeiss Meditec AG; "Photodynamic therapy increases the eligibility for feeder vessel treatment of choroidal neovascularization caused by age-related macular degeneration.", Piermarocchi, S.; Lo-Giudice, G.; Sartore, M.; Friede, F.; Segato, T.; Pilotto, E.; Midena, E.; Am. J. Ophthalmol. 2002 Apr; 133(4): 572-5).

Moreover, all mentioned treatment methods and devices are methods and devices of direct action on the eye tissues. In other words they affect not the reason of the disease but the symptoms^'. Macular degeneration is known to be the disease concerned with the immunodeficiency state of the human.

One of the VISULASTM 690s disadvantages is the necessity to use it in combination with special chemical agent that is toxic and acts as optical sensitizer. Besides to use of such substances it is necessary to provide the special conditions for the patients which can be guaranteed in the in-patient department of the hospital only.

Another disadvantage of this system is its technical complexity caused by the requirements regarding energy density uniformity of irradiation over the affected eye areas. This problem causes sever requirements to the beam forming system and beam control system. The significant technical problem is the laser power control and laser energy stabilization. Furthermore, high coherence of laser radiation predetermines certain difficulties in forming of uniform light field over the affected parts of the retina to be irradiated.

Technical complexity and the special requirements to the operating conditions result in additional professional requirements for medical staff and as a consequence to the higher cost of the service and equipment. The most common shortcoming of existent systems is that they are designed only for the treatment of "wet", neovascular form of macular degeneration. For the ^λλdry" form of the macular degeneration such systems are not effective.

Significant disadvantages of all devices and methods, including, VISULASTM 690s system, are all of them provide the symptomatic treatment of the systemic disease consequences without the impact on the reasons produced the symptoms onset.

Proposed method and device for its realization stimulate the human immunity, resulting in the positive effect on the eye vascular system.

A treatment method of macular degeneration including age-related macular degeneration (AMD) according to the present invention envisages using the special device in special manner for transpupillar irradiation of the patient's retina affected parts with visible and near infrared quasi- monochromatic light pulses with such values of average energy that does not result in irradiated retina tissue coagulation. The correspondent average radiation energy does not exceed 10^"^_Joules per pulse.

The procedures mentioned above may be performed without any chemicals and medical substances being injected to the human body.

The main distinction of the proposed device is the use of LED (light-emitting diode) as the source of radiation. They possess proper characteristics:

• High radiation power (0,01-0,25 microwatt);

• High light output efficience;

• Narrow radiation spectral band (half-width up to 10 nm) ; • Small supply current in comparison with the laser source of radiation (< 0.25 milliampere) ;

• Quasi-linear relation between power of radiation and supply current;

• Small size and weight, simplicity of spatial configuration changing;

• Low cost;

• Market availability at reasonable prices of the wide range of LEDs that emit in the different bands of visible and near infra-red spectral range;

The device according to the invention is a programmed controlled LED source of quasi monochromatic radiation, which preferably consists of of one or more arrays of ultra bright LEDs, which are operating in visible and infra-red spectral ranges. The usage of LED instead of lasers allows increasing stability and controllability of the light source due to strong dependence of LED' s brightness on the supply current. These widely enable to form light pulses with stable, reproducible, established in advance parameters as energy, duration, shape, repetition rate etc.). Also device reliability increases, overall dimensions and weight decrease. The LEDs by themselves in contrast to lasers do not require special technical servicing. Moreover, today LEDs are commercially available and they irradiate in the different bands of visible and near infra-red ranges and cover these ranges almost entirely in distinction from lasers emitting at the fixed wavelengths. Low coherence of LED radiation simplifies a problem of uniform light field forming at those parts of the retina that must be irradiated (in particular, speckle is not occurred) . Necessary uniformity could be achieved by means of LEDs arrangement in the form of array of appropriate configuration. Additionally, in some cases diffusers as light homogenizers can be used. It can be opal glass diffuser for example.

Unlike the lasers, LED's small dimensions and weight, low energy consumption and simplicity of use give the possibility to develop the device that will be easy-to-use, with weight approximately 300-400 g, which has alignment system (special glasses, holders, racks) , and radiation delivery system to the affected organ. The device and the treatment method are easy-to-use and do not require special technical training of medical staff and availability of specific conditions for the procedures. All parameters and the procedure algorithm, including the duration of irradiation, are controlled by software. The staff must only choose algorithm in every special cases. The maintenance costs of the method and the device for macular degeneration treatment is lower in comparison with competitive methods and devices.

The method and the device for its realization are most effective for the "dry", non-neovascular form of MD treatment or visual function stabilization (loss of visual acuity more then 50%) and for the early stages of "wet", neovascular form of macualar degeneration treatment as well.

Regeneration, stabilization and improvement of visual function coincide with experimental data concerning the 15- 20% rise of DNA content in the retina cell nucleolus and with appreciable positive human immune system response to the retina irradiation by the monochromatic light. Consequently, it is contended that the influence is very directed on the reasons of the disease origin lied in the age-specific or artificial immunity suppression.

There is a list of main symptomatic characteristics by which one can diagnose macular degeneration. When using proposed method and device, significant positive changes in visual functions are achieving. The list of symptoms and changes see in the Table 1.

Visual function stimulation, its stabilization and improvement with the presence of MD occur owing to the specific quasi-monochromatic, low-intensity light pulse with selected wavelength action. Experimental studies results have showed that the main reason for visual function stimulation is positive immune system response to the retina irradiation by the monochromatic light. In other words, immune system is stimulated at first, and then as a consequence eye vascular system is improved that in its turn leads to the eye visual function stabilization and regeneration. Radiation with the different wavelengths effects the specific response of the immune system. That is, every radiation wavelength has its own impact result on the immune system (quantitative and qualitative) . Impact effectiveness depends upon the spectral characteristics of the radiation source as well as upon mode of operation. By the mode of operation we understand: irradiation duration, quantity of the irradiation sessions, irradiation energy, light pulse repetition rate, light pulse shape, and quantity of light pulses. All these characteristics combination provides for the most effective response of every immune system components. Proposed device allows realizing each of the needed operation mode for the MD treatment and eye visual function stimulation.

Figure 1 represents device flow chart for MD treatment.

This device consists of a power supply unit 1, indicator and control unit 2, controller 3, LEDs control unit 4, and unit 5

The power supply unit 1 is the storage battery. It has corresponding charger. Electrically charger is connected to the indicator and control unit 2, controller 3, and LEDs control unit 4.

Indicator and control unit 2 is used by operator for the device operation mode selection and for the indication of running status of the device. Specifically, it can display the data concerning all units' readiness for operation, error messages and prompts for operator. Indicator and control unit 2 is connected to the controller 3 electrically.

Controller 3 performs device operation control according to the programs that determine operational algorithm of the device. Also controller 3 performs diodes calibration, monitoring of device operation, emergency protection, record and storage of information concerning date, duration and operating mode of the device. Controller 3 ensures access authorization to the device control. Controller 3 is connected to the indictor and control unit 2 and LEDs control unit 4 electrically.

LEDs control unit 4 transforms the controller commands into current supply pulses of light emitting diodes. Parameters of the current supply pulses correspond to the given control program for the operating mode. Electrically LEDs control unit 4 is connected to the LEDs assembled on the printed circuit board for example as an arrays 6, which are integrated in irradiating light unit 5. The irradiating light unit 5 forms directional pattern of irradiating light and delivers light to one or two eyes of the patient at once. The unit 5 allows to ajust the arrays 6 spatial configuration to provide irradiating light delivering in the most effective way to both eyes at once. The unit 5 is installing stationary or may be holded and adjusted manually by the patient. Housings of LED arrays 6 may be sealed. The unit 5 box is suitable for the disinfection. After the switching on of power supply that is independent storage battery operated, information concerning battery charging condition and power supply switching on indication appears on the display of control and indication unit 2.

Then system self-testing occurs. When the indication "calibration" is on calibration of the light sources performs .

By the testing results the indication of the ready state condition of the device ("Ready" or "Failure") appears.

When this procedure is over the irradiating light unit 5 is optimally arranged with the respect to the patient's eyes.

Appropriate radiation mode is switched on (separate buttons "Mode 1", "Mode 2" etc.). Irradiation is starting up (separate bottom "Start") .

Irradiation occurs according to the operating mode programs previously stored to the controller 3. In compliance with these programs controller 3 manages the following parameters: exposure duration, light pulses amplitude, light pulses duration, light pulse repetition rate, and sequence of the LED radiation with different wavelengths.

Subject to the control programs the device can operated in pulse or continuous wave mode of radiation.

The current supply can vary over the range of 0-40 mA with the step 1 mA.

Exposure period can vary over the range of 0-15 minutes with the step 1 minute.

Light pulses duration can vary over the range from 10 microseconds to 1 second. Light pulse-repetition rate can vary over the range from 0 to 10 kHz. According to the test data, optimum performance for the "dry" macular degeneration treatment is the course consisting of 10 sessions per 5 minutes each being held on out-patient basis three times per year. For that the arrays with LEDs emitting in green (520nm) and infra-red (940nm) spectral areas is used.

The irradiation parameters are as follows: light pulse repetition rate is 30 Hz, light pulses duration is 10 ms, exposition equals to 5 nαin, monochromatic radiation energy lies within the range 10^~6÷10^"5 joules . These energy values are subthreshold, i.e they do not cause coagulation of the irradiated retina tissues. The energy value assorts particularly within the above mentioned range depending on the pigmentation level, refraction and location of the degeneration area.

Treatment effect that consists in improvement of visual function (increase in visual acuity, lessening of central flows in the fields of vision and diminution of its density) became apparent on the next day. Immune response of the human organism becomes evident since the first instant after the irradiation and continue changing during the period of 14 days. For example, immunoregulatory index rises several times (up to 8÷10) . Clinical effect remains during 3÷4 months.

Table 1

Claims

1. A method of the macula degeneration treatment by irradiating of the retina damaged areas through the pupil wherein the technique of the irradiation performed by the quasi-monochromatic light pulse in visible and near infra-red spectral range with energy that does not exceed 10^"5 joules.

2. The method according to claim 1 wherein the irradiation performed according to the program given in advance with the possibility of the synchronous or consecutive irradiation by quasi-monochromatic light in the spectral ranges, with the different pulse duration, different pulse repetition rate, different exposure periods or pulse number, different pulses shape and their relative time delay.

3. The method according to claims 1 and 2 wherein the irradiation performed in combination with the medical drugs use.

4. A device for the macula degeneration treatment that consists of radiation source, radiation directional pattern forming means, means to deliver the radiation to the given part of the retina through the pupil, power supply unit, and indicator and control unit; the device comprising at least one light emitting diode (LED) is used as the source of radiation.

5. The device according to claim 4 wherein LEDs form at least one array of LEDs.

6. The device according to claim 5 wherein the array of LEDs consists of at least 2 groups of LEDs able to radiate in two different spectral bands.

7. The device according to claims 4,5,6 wherein it additionally consists of the programmed controller and LED control unit, where controller electrically connected to the indicator and control unit and to the LED control unit that forms current pulses running through the light emitting diodes .

8. The device according to claims 4,5,6,7 wherein the controller has interface for its programming and it is functioning according to the program, parameters change of which provides for the controller commands sending into the LED control unit in order to provide synchronous or consecutive irradiation by quasi-monochromatic light at the different areas of the range, with the different pulse duration, different pulse repetition rate, different exposure period or pulse quantity, different pulse shape and their relative time delay.

9. The device according to claims 4,5,6,7,8 wherein the LED matrix has form of polygon or oval.

10. The device according to 4,5,6,7,8,9 wherein device for the forming of the directional pattern comprises a radiation diffuser.

11. The device according to claims 4,5,6,7,8,9,10, wherein radiation diffuser is made from the opal glass.